The Role of Exercise-Periodic-Breathing (EPB) in Impaired Ventilation Regulation Dysfunction in Heart Failure Patients

• VO2 max(maximal oxygen consumption) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  During cardiopulmonary exercise test, we could measure the value of patients' maximal oxygen consumption. It could represent the functional level of heart failure patient and be the mortality prediction.
  
  

• EPB pattern [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  We define the exercise periodic breathing pattern in primary cardiopulmonary exercise test(CPET). After exercise intervention, we analyze the ventilation picture again in follow up CPET. (EPB also a morality prediction )
  
  
• All-cause mortality/CV morbidity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  

Patients with heart failure display dyspnea on exertion, lower PCO2 and higher ventilatory response to exercise (V E -V CO 2slope), which demonstrated dysregulation of breathing in this disease category. Some of these patients develop further ventilation dysregulation pattern with ventilatory oscillation composed with exercise periodic breathing (EPB) and sleep apnea. Previous studies revealed the ventilatory oscillation was associated with cyclic changes in arterial oxygen (PO2) and carbon dioxide (PCO2) tensions, and also associated with severely impaired exercise tolerance, a steep V E -V CO 2slope, and low peak O 2 consumption, both correlated with the worse severity of heart failure and adverse prognosis. The origin of ventilatory oscillation might involved instability of the ventilator control system, which composed with prolonged circulatory delay, abnormal peripheral ergoreflex activation and peripheral chemo- and baro-sensitivity, even through abnormal autonomic reflexes to an altered central command. However, the most studies investigated these responses via sleep apnea under resting status especially those about brain. The real-time change response to exercise was limited to ventilatory parameters such as oxygen consumption, carbon dioxide production. Whether the exercise periodic breathing response to exercise which lead to abnormal cerebral hemodynamic responses to exercise in HF remain unclear.

Impaired cerebral blood flow was demonstrated during apnetic episode and related to neuropsychological deficits in sleep apnea patient. To be controlled by the same key feedback mechanism, impaired cerebral blood flow during exercise in EPB patients could be speculated. Moreover, Cerebral hypo-perfusion responses to exercise may contribute to the impairment of functional capacity in patients with HF. Accordingly, we hypothesize that the abnormal cerebral hemodynamics by exercise periodic breathing during exercise is associated with the decline of functional capacity in patients with HF. Besides, Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.

We will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. We expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. Sixty HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. We will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics (percentage, mean, and standard deviation), independent t-test, and repeated measure ANOVA. We study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.

This study employed simultaneously a noninvasive, bio-reactance device (i.e., noninvasive continuous CO monitoring system, NICOM) to assess cardiac hemodynamics, and a near-infrared spectroscopy (NIRS) to monitor changes in cerebral and muscular perfusion/oxygenation. We further elucidated the real-time adaption between ventilator parameter and hemodynamic ones during ventilation oscillation in patients with HF.